Andrew James Paterson (b. 1951, Christchurch, New Zealand), citizen of the U.S.A. He received his MSc (Chemistry) from the University of Canterbury in 1975, and a PhD (Biochemistry) from the University of Otago, New Zealand in 1981. In 1981 he joined the postdoctoral fellowship program at the NIH (NCI) for 3 years and then moved to Toronto Canada as Research Associate in Dr Jeffrey Kudlow’s laboratory. In 1989 he came to UAB as Assistant Professor joining the Department of Medicine, Division of Endocrinology, with Dr. Kudlow as division director. He continued work on growth factor regulation and how O-Glycosylation regulates cellular function.

Role of O-Glycosylation in Gene Regulation, Cell Growth, and Differentiation.

Description

The research in our laboratory is focused on the regulation of cell function by the O-GlcNAc post-translational modification on cellular proteins. We showed that the regulation of transforming growth factor-α gene expression by glucose was linked to the O-GlcNAc status of the ubiquitous transcription factor, Sp1. Thus, glucose-specific O-GlcNAc modification of Sp1 regulated not only TGF-α, but also a multitude of other cytoplasmic and nuclear proteins, including the proteasome, a major protein complex whose function is to get rid of unwanted cellular proteins. Our data showed that increased cellular O-GlcNAc levels reduced proteasome activity, and since some of the important cellular regulatory proteins, such as Sp1, p53, IκB, and the cyclins, are targets of the proteasome, they too can be regulated by glucose. For example, in times of low nutrition (less O-GlcNAc modification), the active proteasome degrades proteins involved in cell propagation (such as Sp1), and processes muscle proteins that are then used as an energy source. Much of our studies have involved the two principle enzymes that regulate the O-GlcNAcylation process; O-GlcNAc transferase (OGT), the enzyme that adds the O-GlcNAc moiety to proteins, and the O-GlcNAcase that removes the modification. Also, these enzymes have an additional function in that they are able to co-associate to regulate gene transcription. In particular, we showed in cell culture that nuclear hormone receptors could be suppressed or activated depending on the O-GlcNAc status of transcription factors, and that mammary tissue development was retarded in a transgenic mouse model through the suppression of estrogen receptor-dependent transcription. We have shown physiological function of modifying O-GlcNAc in other tissues, including, brain, eye and muscle, linking the phenotypes to various degenerative diseases.